麋鹿角调控慢性压力应激小鼠神经营养因子和压力应激因子抗抑郁作用研究＊

目的 考察麋鹿角提取物调控神经营养因子和压力因子抗抑郁的作用机制。方法 制备麋鹿角提取物,采用小鼠慢性应激压力（chronic unpredictable mild stress,CUMS）模型,通过糖水偏嗜实验、悬尾实验和强迫游泳实验评价麋鹿角提取物的抗抑郁功效。采用ELISA法测定受试动物海马区中神经生长因子（Nerve growth factor,NGF）、脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）的含量。采用ELISA测定受试动物血清中相应压力因子：促肾上腺皮质激素释放激素（corticotropinreleasing factor,CRF）、促肾上腺皮质激素（adreno-cortico-tropic-hormone,ACTH）、皮质醇的含量。采用大鼠星形胶质瘤细胞（C6）评价麋鹿角提取物调控神经营养因子系统的作用,并采用小鼠海马永生化细胞系（HT22）评价其对抗压力因子损伤的作用。结果 麋鹿角提取物能显著上调模型小鼠糖水偏嗜率,缩短小鼠悬尾和强迫游泳不动时间,以麋鹿角水提物的效用最强,该提取物能通过Erk信号通路,显著上调C6细胞中的NGF和BDNF的表达。此外,在皮质醇（Cortisol）损伤HT22的体外模型中,麋鹿角水提物具有显著的细胞保护作用,效果优于醇提物。结论 麋鹿角对神经营养因子的调控和压力因子的调控是其抗抑郁的重要机制。

Researches on Anti-depression Mechanism of Elk Antler via Regulation of Neurotrophic Factors and Stress Factors on Chronic Unpredictable Mild Stress Induced Mice

Objective To investigate the mechanism of elk antler exerting anti-depression effect via regulation of neurotrophic factors and stress factors. Methods Elk antler extracts were prepared with water or ethanol. The anti-depressive effects of elk antler extracts were evaluated on chronic unexpected mild stress (CUMS) induced depression-like mice by sucrose preference test, tail suspension test and forced swimming test. The expressions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in hippocampus were determined by ELISA. The amounts of corticotrophin releasing hormone (CRF), adrenocorticotropic hormone (ACTH) and corticosterone (Cort) were also determined in serum by ELISA. Rat astroglioma cell lines (C6) were used to evaluate the effect of elk antler on regulating neurotrophic factor expressions. Mouse hippocampal immortalized cell lines (HT22) were established to evaluate the protective effect of the elk antler on stress neuronal damages. Results Elk antler extracts could significantly increase sucrose preference rate and decrease the immobile time of tail suspension and forced swimming on CUMS induced depression-like mice and the water extracts show the better effect. The water extract of elk antler could significantly increase the expressions of NGF and BDNF on C6 cells via Erk-dependent signaling pathway. In addition, the water extract of elk antler could protect HT22 neuronal cells from cortisol damages. The effect of water extracts was also superior to ethanol extracts. Conclusion Regulation of neurotrophic factors and stress factors might contribute to the anti-depressive effect of elk antler.